Over the last few years, protocols have been established to develop the ?next generation? of cancer models, in vitro propagating cultures that can be verified to more closely represent the tumor from which they originated. Several groups have demonstrated that organoid cultures and conditionally reprogrammed cells in combination with unique media formulations offer new tools to address current gaps in our understanding of cancer initiation, development, and progression. Systematic application of these novel culture methods now present an opportunity to develop a large library of cancer models that can be made available as a community resource to investigators in academia and the biopharmaceutical industry. In response to the opportunity, the National Cancer Institute?s (NCI) Office of Cancer Genomics (OCG), in the Center for Cancer Genomics (CCG), together with international institutions, has established a consortium, the Human Cancer Models Initiative (HCMI). HCMI?s goal is to make available to the scientific community large numbers of ?next generation? in vitro cancer models that are not encumbered with excessive intellectual property (IP) constraints. To support the US contribution to HCMI, OCG established two Cancer Model Development Centers (CMDC) to develop the ?next generation? models using high-throughput, systematic techniques. The CMDC sites have established relationships with their own network of clinical sites at which cancer patients will be consented and enrolled to donate their medical data and tissues. Eventually, successfully developed models will be made available via a third-party distributor, and the case-specific clinical and molecular characterization data will be made available through CCG?s Genomic Data Commons (GDC, https://gdc.nci.nih.gov/index.html).